Comparison of two methods for tumour-targeting peptide modification of liposomes  

作　　者：Shi-qi Huang Han-ming Zhang Yi-cong Zhang Lu-yao Wang Zhi-rong Zhang Ling Zhang 

机构地区：[1]Key Laboratory of Drug Targeting and Drug Delivery Systems,Ministry of Education,West China School of Pharmacy,College of Polymer Science and Engineering,Med-X Center for Materials,Sichuan University,Chengdu 610041,China

出　　处：《Acta Pharmacologica Sinica》2023年第4期832-840,共9页中国药理学报（英文版）

基　　金：supported by the National Natural Science Foundation of China(Nos.81690261,82022070 and 81872824);the Medico-Engineering Cooperation Programme from the Med-X Center for Materials,Sichuan University(MCM202103).

摘　　要：Liposomes decorated with tumour-targeting cell-penetrating peptides can enhance specific drug delivery at the tumour site.The TR peptide,c(RGDfK)-AGYLLGHINLHHLAHL(Aib)HHIL,is pH-sensitive and actively targets tumour cells that overexpress integrin receptorα_(v)β_(3),such as B16F10 melanoma cells.Liposomes can be modified with the TR peptide by two different methods:utilization of the cysteine residue on TR to link DSPE-PEG2000-Mal contained in the liposome formula(LIP^(TR))or decoration of TR with a C18 stearyl chain(C18-TR)for direct insertion into the liposomal phospholipid bilayer through electrostatic and hydrophobic interactions(LIP^(C18-TR)).We found that both TR and C18-TR effectively reversed the surface charge of the liposomes when the systems encountered the low pH of the tumour microenvironment,but LIP^(C18-TR) exhibited a greater increase in the charge,which led to higher cellular uptake efficiency.Correspondingly,the IC_(50) values of PTX-LIP^(TR) and PTX-LIP^(C18-TR) in B16F10 cells in vitro were 2.1-fold and 2.5-fold lower than that of the unmodified PTX-loaded liposomes(PTX-LIP),respectively,in an acidic microenvironment(pH 6.3).In B16F10 tumour-bearing mice,intravenous administration of PTX-LIP^(TR) and PTX-LIP^(C18-TR)(8 mg/kg PTX every other day for a total of 4 injections)caused tumour reduction ratios of 39.4%and 56.1%,respectively,compared to 20.8%after PTX-LIP administration.Thus,we demonstrated that TR peptide modification could improve the antitumour efficiency of liposomal delivery systems,with C18-TR presenting significantly better results.After investigating different modification methods,our data show that selecting an adequate method is vital even when the same molecule is used for decoration.

关 键 词：liposomes C18-TR TR tumour-targeting cell-penetrating peptides B16F10 melanoma cells 

分 类 号：R730[医药卫生—肿瘤]